This laboratory has studied the molecular basis of embryogenesis in Xenopus laevis and the zebrafish, with special emphasis on axis determination and pattern formation. These events are thought to be controlled by cell-to-cell signaling and by the spatially and temporally regulated action of transcription factors. The Wnt family of signaling molecules is involved in developmentin many ways. An important component of Wnt signaling is the interaction between Wnt factors and soluble antagonists which can modulate the signal. In collaboration with the laboratory of Jeremy Nathans at John Hopkins University, a novel Wnt-binding factor, named WIF-1, has been characterized. WIF-1 binds some but not all Wnt factors and inhibitis their biological function in vivo. WIF-1 is highly conserved among vertebrates and is expressed in early somite formation where it appears to be required for normal somitogenesis. The Xlim-1 gene encodes a LIM- homeodomain protein that has been shown to be involved in the functions of the Spemann organizer in neural induction and mesoderm patterning. Studies on the regulation of Xlim-1 expression by ativin have shown previously that the activin response element is located in the first intron. Recent work in collaboration with the laboratory of Malcolm Whitman at Harvard Medical School showed that binding sites for the signal transducing component Smad4 and the forkhead class protein FAST-1 are required for activin regulation of Xlim-1 expression.A screen for developmentally regulated genes is being conducted in zebrafish. In this screen, randomly picked cDNA clones are subjected to in situ hybridization, and clones showing differential expression patterns are further characterized. One aim of this project is to generate candidate genes for the cloning of mutations that have been identified in zebrafish. For this purpose, a convenient mapping approach is required, and radiation hybrid (RH) mapping has been chosen as appropriate. In collaboration with several groups of researchers a new RH mapping panel has been established and a framework map generated that allows rapid placement of zebrafish cDNA or genomic sequences. This mapping tool is available to the zebrafish research community on the Laboratory Web Site. - Frog, Zebrafish, Embryogenesis, Axis Formation, Induction, Radiation Hybrid Mapping